title: Prolonged cultivation of hippocampal neural precursor cells shifts their differentiation potential and selects for aneuploid cells.
abstract: Neural precursor cells (NPCs) are lineage-restricted neural stem cells with limited self-renewal, giving rise to a broad range of neural cell types such as neurons, astrocytes, and oligodendrocytes. Despite this developmental potential, the differentiation capacity of NPCs has been controversially discussed concerning the trespassing lineage boundaries, for instance resulting in hematopoietic competence. Assessing their in vitro plasticity, we isolated nestin+/Sox2+, NPCs from the adult murine hippocampus. In vitro-expanded adult NPCs were able to form neurospheres, self-renew, and differentiate into neuronal, astrocytic, and oligodendrocytic cells. Although NPCs cultivated in early passage efficiently gave rise to neuronal cells in a directed differentiation assay, extensively cultivated NPCs revealed reduced potential for ectodermal differentiation. We further observed successful differentiation of long-term cultured NPCs into osteogenic and adipogenic cell types, suggesting that NPCs underwent a fate switch during culture. NPCs cultivated for more than 12 passages were aneuploid (abnormal chromosome numbers such as 70 chromosomes). Furthermore, they showed growth factor-independent proliferation, a hallmark of tumorigenic transformation. In conclusion, our findings substantiate the lineage restriction of NPCs from adult mammalian hippocampus. Prolonged cultivation results, however, in enhanced differentiation potential, which may be attributed to transformation events leading to aneuploid cells.
authors.forename: The Duy
authors.initials: TD
authors.lastname: Nguyen
authors.forename: Darius
authors.initials: D
authors.lastname: Widera
authors.forename: Johannes
authors.initials: J
authors.lastname: Greiner
authors.forename: Janine
authors.initials: J
authors.lastname: Müller
authors.forename: Ina
authors.initials: I
authors.lastname: Martin
authors.forename: Carsten
authors.initials: C
authors.lastname: Slotta
authors.forename: Stefan
authors.initials: S
authors.lastname: Hauser
authors.forename: Christian
authors.initials: C
authors.lastname: Kaltschmidt
authors.forename: Barbara
authors.initials: B
authors.lastname: Kaltschmidt
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000782:Aneuploidy; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism